Cells In Gut-associated Lymphoid Tissue Research Articles

T cell regulation of IgA immunoglobulin production in gut-associated lymphoid tissues

To explore mechanisms of gut-mucosal IgA immune response, we have established Con A-induced cloned T cell lines originating from PP and spleen. These cloned cells expressed Thy-1.2 +, Lyt-1 +2 −, Ia (I-A and I-E) and H-2 (K/D) surface antigens. Cloned T cells derived from PP were found to suppress LPS-induced IgM and IgG synthesis and secretion of co-cultured PP B cells; in addition, whereas the PP cloned T cells did not bring about IgA production, they did cause the appearance of large numbers of cells expressing sIgA. In contrast, cloned T cells derived from spleen had little or no effect on LPS-induced IgM synthesis and secretion by PP B cells; in addition, whereas they did suppress IgG production, they neither brought about IgA production nor the appearance of cells expressing sIgA. These studies provide evidence for the existence of a new type of T cell in PP, a switch T cell, which is able to induce B cells to undergo class-specific switches from IgM to IgA; the PP switch T cells appear to govern the pathway of DNA recombination (or RNA splicing) rather than cellular events resulting in terminal differentiation. Thus, these switch T cells are probably responsible for the fact that PP are a major source of mucosal IgA B cells. In additional studies, we show that post-switch IgA B cells, i.e. cells precultured with PP cloned T cells, have the capacity to undergo terminal differentiation into IgA producing plasma cells. provided they are exposed to helper T cells (uncloned) and an appropriate mitogenic stimulus (staphylococcal protein A). We can conclude, therefore, that the development of PP B cells into IgA-producing plasma cells in gut-associated lymphoid tissues (GALT) appears to require at least two steps: one which involves heavy chain switching to IgA and which is governed by IgA class-specific switch T cells in PP, and one which involves differentiation of post-switch B cells and which is governed by helper T cells in lymphoid tissues outside of PP (such as MLN and spleen).

Orally Induced Tolerance

Abstract Mattingly and Waksman have recently reported clear-cut and convincing data demonstrating the formation of antigen-specific suppressor cells in gut-associated lymphoid tissue (GALT) after oral administration of antigen (1). To consider formation of suppressor cells in GALT as an independent process responsible for orally induced tolerance, however, is to ignore information specifically implicating the liver in the induction of this tolerance. Thus, the authors overlook the fact that direct intraportal injection of sheep erythrocytes (2), bovine γ-globulin (3), or picryl chloride (3) renders susceptible animals immunologically unresponsive to these materials, and that the tolerogenic effect of oral feeding of a simple chemical antigen is abolished by diverting portal flow from the liver (4). The precise mechanism responsible for immunologic unresponsiveness after portal circulation of antigen to the liver is unknown but in several of the papers cited by Mattingly and Waksman, the following possibilities are considered: 1) the liver may sequester immunogenic fragments of antigen-antibody complexes and thus allow tolerogenic components to exert their effect (5); 2) intrahepatic portal lymphoid tissue may form IgA that joins with absorbed antigen to suppress immunologically active cells (6); 3) induction of suppressor cells may require access of antigen to liver (7).

Appendix and γM-antibody formation: VII. Rosette-forming cells in rabbits immunized with sheep erythrocytes

After intravenous immunization with sheep red blood cells the rabbit spleen shows a sharp rise in the number of plaque-forming cells but there is no detectable rise in PFC in the appendix or mesenteric lymph node of the same animals. Repeated immunization via an appendicostomy blind loop results in virtually no local PFC and only a small rise in splenic PFC. In lethally irradiated animals neither thymocytes nor appendix cells alone restore the splenic PFC response. Simultaneous injection of the two cell types restores both direct and indirect plaque formation. The injected cells were labeled with tritiated adenosine and a standard rosette assay for specific antigen-binding cells applied to recipients' spleen cells following immunization. Rosettes appeared by 3 days after immunization whether thymocytes or appendix cells were labeled. Labeled rosettes were observed only in animals receiving labeled appendix cells. This result demonstrates the presence of rosette forming cell precursors in rabbit appendix cell populations and suggests that the cells of gut-associated lymphoid tissues include antibody-forming cell precursors which are normally seeded to the spleen and draining lymph nodes.